Objectives: The purpose of this study was to confirm the effects of Liriope platyphylla extract on relieving Gastroesophageal reflux disease (GERD) through regulation of acid secretion. Methods: 8-week-old ICR mice were divided into untreated control group (Ctrl), GERD elecitation group (GERDE), Omeprazole administrate group before GERD elicitation (OMA), and Liriope platyphylla extract administrate group before GERD elicitation (LPA). After inducing GERD, gross observation and histological examination were performed and ATP6V1B1 (ATPase H+ Transporting V1 Subunit B1), GRPR (Gastrin-releasing peptide receptor), COX-1 (Cyclooxygenase 1), 8-OHdG (8-hydroxy-2'-deoxyguanosine), Cathelicidin, p-JNK (phospho c-Jun N-terminal kinase) were observed to confirm the damage defense effect of the esophageal mucosa, acid secretion regulation, antioxidant, anti-inflammatory, mucosal protection, and apoptosis regulation Results: OMA and LPA showed lower levels of damage compared to GERDE in gross observation and histological examination. ATP6V1B1, GRPR, and 8-OHdG showed lower positive reactions in OMA and LPA than in GERDE. COX-1 were less positive in GERDE and OMA than in Ctrl, but showed higher secretion in LPA than in Ctrl. Cathelicidin showed a decreased positive reaction in GERDE, OMA and LPA compared to Ctrl, but the decrease in positive reaction was smaller in OMA and LPA compared to GERDE. p-JNK showed increased positive reaction in GERDE, OMA and LPA than in Ctrl, but the increase in the positive reaction was smaller in the OMA and LPA compared to GERDE. Conclusions: The effects of Liriope platyphylla extract on esophageal mucosal damage protection, acid secretion regulation, antioxidant, anti-inflammatory, mucosal protection and apoptosis regulation were confirmed.
Changes in ATP and related compounds, TMAO, TMA, creatine and creatinine were analyzed to establish the processing conditions for rapid- and low salt-fermented liquefaction of anchovy(Engrulis japonica) extracts during fermentation. Experimental sample A: chopped whole anchovy, adding 20% water, heating at $50^{\circ}C$ for 9 hrs and then adding 10% NaCl. Sample B: chopped whole anchovy, adding 20% water, heating at $50^{\circ}C$ for 9 hrs and then adding 13% NaCl. Sample C: chopped whole anchovy adding 13% NaCl. Sample D: whole anchovy adding 17% NaCl. ATP, ADP, AMP and IMP were broken down during fermentation period, while inosine and hypoxanthine or hypoxanthine were detected in each fermented liquefaction of anchovy. However the amounts of them were varied from collection to collection according to the pretreatment methods. Possibly ATP and their related compounds will not make a great contribution to the umami taste in fermented liquefaction of anchovy. The contents of TMAO were decreased during fermentation period, ranging from 3 to 15 mg/100g in the fermented liquefaction of anchovy after 180 days. The TMA contents were increased slowly during fermentation period, ranging from 60 to 114 mg/100g in the 180 days specimens, however their contents were varied from sample to sample. The contents of creatine and creatinine were increased during early fermentation period, and then they were decreased in the last period. As for distribution of nitrogen in the anchovy extracts, the contribution of creatine and creatinine to the extractive nitrogen was occupying 6.8, 5.7, 4.6 and 5.7% in the experimental sample A, B, C and D, respectively. The contribution of ATP and related compounds to the extractive nitrogen was occupying 2.1, 2.4, 2.2 and 2.7% in the experimental sample A, B, C and D, respectively. The contribution of TMAO and TMA to the extractive nitrogen was very low as they are occupying $0.7{\sim}1.2%$ in the four experimental samples.
Objective: Pathogenesis of the endometriosis is very complex and the etiology is still unclear. Our hypothesis is that there may be some difference in gene expression patterns between eutopic endometriums with or without endometriosis. In this study, we analyzed the difference of gene expression profile with cDNA microarray. Methods: Endometrial tissues were gathered from patients with endometriosis or other benign gynecologic diseases. cDNA microarray technique was applied to screen the different gene expression profiles from early and late secretory phase endometria of those two groups. Each three mRNA samples isolated from early and late secretory phase of endometrial tissues of control were pooled and used as master controls and labeled with Cy3-dUTP. Then the differences of gene expression pattern were screened by comparing eutopic endometria with endometriosis, which were labeled with Cy5-dUTP. Fluorescent labeled probes were hybridized on a microarray of 4,800 human genes. Results: Twelve genes were consistently over-expressed in the endometrium of endometriosis such as ATP synthase H transporting F1 (ATP5B), eukaryotic translation elongation factor 1, isocitrate dehydrogenase 1 (NADP+), mitochondrial ribosomal protein L3, ATP synthase H+ transporting (ATP5C1) and TNF alpha factor. Eleven genes were consistently down-regulated in the endometriosis samples. Many extracellular matrix protein genes (decorin, lumican, EGF-containing fibulin-like extracellular matrix protein 1, fibulin 5, and matrix Gla protein) and protease/protease inhibitors (serine proteinase inhibitor, matrix metalloproteinase 2, tissue inhibitor of metalloproteinase 1), and insulin like growth factor II associated protein were included. Expression patterns of selected eight genes from the cDNA microarray were confirmed by quantitative RT-PCR or real time RT-PCR. Conclusion: The result of this analysis supports the hypothesis that the endometrium from patients with endometriosis has distinct gene expression profile from control endometrium without endometriosis.
Obesity is an epidemic disease characterized by an increased inflammatory state and chronic oxidative stress with high levels of pro-inflammatory cytokines and lipid peroxidation. Moreover, obesity alters cholesterol metabolism with increases in low-density lipoprotein (LDL) cholesterols and triglycerides and decreases in high-density lipoprotein (HDL) cholesterols. It has been shown that mulberry leaf and fruit ameliorated hyperglycemic and hyperlipidemic conditions in obese and diabetic subjects. We hypothesized that supplementation with mulberry leaf combined with mulberry fruit (MLFE) ameliorate cholesterol transfer proteins accompanied by reduction of oxidative stress in the high fat diet induced obesity. Mice were fed control diet (CON) or high fat diet (HF) for 9 weeks. After obesity was induced, the mice were administered either the HF or the HF with combination of equal amount of mulberry leaf and fruit extract (MLFE) at 500mg/kg/day by gavage for 12 weeks. MLFE treatment ameliorated HF induced oxidative stress demonstrated by 4-hydroxynonenal (4-HNE) and modulated the expression of 2 key proteins involved in cholesterol transfer such as scavenger receptor class B type 1 (SR-B1) and ATP-binding cassette transporter A1 (ABCA1) in the HF treated animals. This effect was mainly noted in liver tissue rather than in cutaneous tissue. Collectively, this study demonstrated that MLFE treatment has beneficial effects on the modulation of high fat diet-induced oxidative stress and on the regulation of cholesterol transporters. These results suggest that MLFE might be a beneficial substance for conventional therapies to treat obesity and its complications.
Numerous biochemical molecules have been implicated in the development of muscular atrophy. However, control mechanisms associated with muscular disease are not clear. The present study was conducted to investigate gene expression profiles of rat muscle during the denervation to atrophy transition processes. We isolated total RNA from rats suffering from partial muscle atrophy (P) and electromyostimulated atrophy (PE) and synthesized cDNA using annealing control primers. Using 20 ACPs for PCR, we cloned 18 DEGs using TOPO TA cloning vector, sequenced, and analyzed their identities using BLAST search. Sequences of 14 clones significantly matched database entries, while one clone was ESTs, and 3 clones were unidentified. Different expression profiles of selected DEGs between P and PE were confirmed. The troponin T, Fkbp1a, RGD1307554, Phtf1, Atp1a1 and Commd3 were highly expressed genes in the P and PE groups, while Krox-25 and TCOX2 were only expressed genes in the P group, the Sv2b and Marcks were only expressed genes in PE group. also, Cox8h was highly expressed genes in PE groups. The ASPH, ND1, and ARPL1 were highly expressed genes in the P and PE groups. List of genes obtained from the present study might provide an insight for the study of mechanism regulating muscle atrophy and electrostimulated muscle atrophy transitions. These data suggest that troponin T, Fkbp1a, RGD1307554, Phtf1, Atp1a1, and Commd3 are potentially useful as clinical biomarkers of age-related muscle atrophy and dysfunction.
Streptococcus mutans (S. mutans), which plays a major role in the etiology of human dental caries, is able to tolerate exposure to acid shock in addition to its acidogenicity. We investigated the effects of pH stress on membrane fluidity, activities and expression levels of F-ATPase, and proton permeability in S. mutans. Using 1,6-diphenyl-1,3,5-hexatriene, we observed membrane ordering at pH 4.8 and pH 8.8. The ordering effects were larger at pH 4.8 in cytoplasmic membranes isolated from S. mutans (CMSM). Increasing pH resulted in a decrease in the activities and expression levels of F-ATPase. The proton permeability was decreased at both acidic and alkaline pHs, and the lowest permeability was observed at pH 4.8. The lower permeability at pH 8.8 than pH 6.8 is likely to be caused by the decreased proton influx due to the decreased CMSM fluidity. In addition, it seems to be evident that extremely low permeability at pH 4.8 was caused by the decreased proton influx due to the decreased CMSM fluidity as well as the increased proton efflux due to the increased activity and expression level of F-ATPase. It is likely that CMSM fluidity and F-ATPase activity are two major key factors that determine proton permeability in S. mutans. We suggest that CMSM fluidity plays an important role in the determination of proton permeability, which sheds light on the possibility of using nonspecific membrane fluidizers, e.g., ethanol, for anti-caries purposes.
Journal of the Korea Academia-Industrial cooperation Society
/
v.12
no.8
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pp.3541-3546
/
2011
Autophagy is an evolutionarily conserved lysosomal pathway for degrading cytoplasmic proteins, macromolecules, and organelles in addition to recycling protein and ATP synthesis. Although autophagy is very important during embryogenesis, the mechanism underlying the dynamic development during this process remains largely unknown. In order to obtain insights into autophagy in early embryo development, we analyzed gene expression levels of autophagy-related genes (ATGs) in mouse embryos developing in vitro. Using real time RT-PCR technique, ATGs including Atg2a, Atg3, Atg4b, Atg5, Atg6, Atg7, Atg9a, and Wipi3, as maternal transcripts, were only up-regulated in 1-cell embryo stage before zygotic genomic activation (ZGA), and then expression decreased from 2-cell to blastocyst embryo stage. ATGs including Dram and Atg9b were expressed abundantly in 1-cell embryo state and in blastocyst embryo stage, athough Atg8 and Ulk1 were constantly expressed during preimplantation stage. However, Atg4d were only up-expressed from 4-cell to blastocyst stage. These results suggest that autophagy is related in mouse embryo, which possibly gives an important role for early development.
Superprecipitation of actomyosin has been considered to be an in vitro model of the muscle contraction. The superprecipitation and ATPase activity (which supplies the energy for contraction) are influenced by several factors which are the large amount of changes in ionic strength, Mg and ATP concentrations. But those behaviors are found to be promptly influenced by the change in a small range of calcium concentration which can be controlled by the cellular function of muscle physiologically only in the presence of the modullatory proteins, tropomyosin and troponin. In order to elucidate the precise roles of calcium in the muscle contraction and relaxation, the effects of calcium on the actin- myosin interaction was observed in the presence of tropomyosin and troponin using the superprecipitation system. The results are summarized as follows: 1. EGTA (glycol ether diaminetetraacetic acid)prolonged the initiation of the superprecipitation of natural actomyosin. 2. Superprecipitation curve was declined by adding EGTA at the time when tile curve reached the half- maximum. The degree of declining was proportional to the amount of EGTA added. Especially, upon adding 0.25 mM EGTA the curve was lowered to the level before the protein superprecipitated. But addition of EGTA did not affect the curve after attaining the maximum. 3. Superprecipitation of Perry myosin B was not affected by EGTA added both before and during the course of the reaction. 4. Tropomyosin did not change the response of Perry myosin B to EGTA added at any time of the reaction. 5. Troponin also did not change the response of Perry myosin B to EGTA. 6. Both tropomyosin and troponin together rendered the Perry myosin B to obtain the same response as natural actomyosin to EGTA. 7. It was concluded that actin-myosin interaction was influenced by the minute change of calcium concentration only in the presence of both tropomyosin and troponin. We could reproduce the contraction and relaxation of the muscle in vitro under the presence of ATP by changing the calcium concentration.
The purpose of present study is to investigate the influence of a spinal gamma-aminobutyric acid B($GABA_B$) receptor on a central regulation of blood pressure(BP) and heart rate(HR), and to define its mechanism in the spinal cord. In urethane-anesthetized, d-tubocurarine-paralyzed and artificially ventilated male Sprague-Dawley rats, intrathecal administration of drugs were carried out using injection cannula(33-gauge stainless steel) through the guide cannula(PE 10) which was inserted intrathecally at lower thoracic level through the puncture of a atlantooccipital membrane. Intrathecal injection of an $GABA_B$ receptor agonist, baclofen(30, 60, 100 nmol) decreased both BP and HR dose-dependently. Pretreatment with 8-bromo-cAMP(50 nmol), a cAMP analog, or glipizide(50 nmol), a ATP-sensitive $K^+$ channel blocker, attenuated the depressor and bradycardic effects of baclofen(100 nmol), but not with 8-bromo-cGMP(50 nmol), a cGMP analog. These results suggest that the $GABA_B$ receptor in the spinal cord plays an inhibitory role in central cardiovascular regulation and that this depressor and bradycardic actions are mediated by the decrease of cAMP via the inhibition of adenylate cyclase and the opening of $K^+$ channel.
Park, Ji-Wan;Uhmm, Saan-Yong;Shin, Chol;Cho, Nam-H.;Cho, Yoon-Shin;Lee, Jong-Young
Genomics & Informatics
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v.8
no.3
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pp.108-115
/
2010
Hypertension is the most prevalent disease worldwide and is itself a risk factor for cerebral, cardiac, and renal diseases. The inconsistency of candidate genes suggested by previous genomewide association studies (GWASs) may be due to not only differences in study design and genetic or environmental background but also the difference in the power of analysis between continuous traits and discrete traits. We analyzed 352,228 single nucleotide polymorphisms (SNPs) in 8842 unrelated Koreans obtained from Ansan and Ansung cohorts. We performed a series of GWA analyses using three different phenotype models; young hypertensive cases (278 subjects) versus elderly normotensive controls (680 subjects); the upper 25% (2211 hypertensive cases) versus the lower 25% of the SBP distribution (2211 hypotensive controls); and finally SBP and DBP as continuous traits (8842 subjects). The numbers of young hypertensive cases and elderly normotensive controls were not large enough to achieve genomewide significance. The model comparing the upper 25% subjects to the lower 25% of subjects showed a power that was approximate to that of QTL analysis. Two neighboring SNPs of the ATP2B1 gene, rs17249754 (SBP, p=$2.53^{-10}$; DBP, p=$1.28{\times}10^{-8}$) and rs7136259 (SBP, p=$1.30{\times}10^{-9}$; DBP, p=$6.41{\times}10^{-8}$), were associated with both SBP and DBP. Interestingly, a SNP of the RPL6 gene, rs11066280, revealed a significant genomewide association with SBP in men only (p=$3.85{\times}10^{-8}$), and four SNPs located near the MAN2A1 gene showed a strong association with DBP only in elderly men aged 60-70 years (e.g., rs6421827, p=$4.86{\times}10^{-8}$). However, we did not observe any gene variant attaining genomewide significance consistently in the three phenotype models except for the ATP2B1 gene variants. In general, the association signal with blood pressure was stronger in women than in men. Genes identified in GWASs are expected to open the way for prevention, early diagnosis, and personalized treatment of hypertension.
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